Biotech yeast project explores mechanics of shmoo

Published 4:00 am, Monday, August 19, 2002

In their offices overlooking the downtown Berkeley BART station, they plan to spend the next five years studying in mathematical detail the mating rituals of yeast.

"Yeast comes in two sexes," said Roger Brent, president of the nonprofit think-tank. They don't lead a very interesting life, he says, but sex is one of the benefits.

Using a newly announced $15.5 million grant from the Human Genome Project, Brent will enlist 40 academic scientists, including UC Berkeley chemistry Professor Julie Leary, in an effort that exemplifies the fundamental premise of biotechnology.

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When biotech scientists study people, mice, fruit flies or yeast, they view their subjects as machines. Complex machines no doubt, but machines nevertheless, in which DNA plays the role of the master controller and RNA serves as its manufacturing arm, churning out the proteins that are the gears, motors, switches and transistors of every living thing.

The Human Genome Project was hailed as an important advance in understanding the workings of the body. But it is only a baby step toward achieving the sort of mathematical formulas that engineers use to design and troubleshoot ordinary machines. The automaker who wants to build a bumper capable of surviving a fender-bender knows the impact characteristics of a given thickness of steel, for instance.

But organisms are so complex, their parts so minuscule, that scientists are only beginning to grasp what happens when the proteins inside a cell interact to accomplish a task such as firing a nerve cell or flexing a muscle.

And though they know roughly how these molecular mechanisms transpire, so far scientists can't compute the forces that enable proteins to do the cell's work -- or stop them from carrying out a necessary task. In short, they want to understand exactly what molecular conditions make us healthy or sick.

But even for the scientists who mapped the genome, discovering the mathematics of life is such a daunting task that Brent's groundbreaking project targets one of the simplest, most widely observed phenomena in biology -- the protein interactions through which yeast cells decide whether or not to mate.

Though they may seem like indistinguishable blobs under the microscope, the two mating types of yeast, which scientists call A and Alpha, literally ooze sexuality at the molecular level. To be more precise, Brent said, yeast cells emit and receive pheromones, the name given to the proteins that transmit sexual signals.

As Brent explained it, yeast cells are choosy about mating. When one yeast cell captures an interesting pheromone, the recipient goes through a decision- making process. If food is plentiful, the yeast may forgo sex and keep chowing down.

But when the mood is right, the receiving yeast cell will signal back to accept the offer. The mating yeast will then begin making "shmoo tips" -- a term playfully derived from the character in the "Li'l Abner" cartoon strip. These schmoo tips are protuberances that grow toward one another until the two yeast cells have fused into one.

"There are about a dozen proteins and a couple of hundred known interactions in this process," Brent said.

In scientific terms, this type of process is called a g-protein coupled pathway. Yeast cells have only one g-protein coupled pathway, the one they use to decide whether or not to shmoo.

But evolution has taken this basic set of protein interactions and greatly expanded its use in higher organisms, such as Chronicle readers.

When we see or smell, for instance, the molecular underpinnings are g- protein processes. When we get frightened and adrenaline rushes through our blood, the molecular upshot is a flood of g-protein signals that prepare the muscles and lungs to fight or flee. Many cancers involve g-protein malfunctions.

"You and I have 2,000 different g-protein coupled receptors," Brent said. "About half of the dollar volume of all the drugs developed today involve g- protein coupled receptors."